A prospective study of 394 infertile men was conducted over 3 years following a primary semen analysis. The cumulative pregnancy rate was 43 and 64% after 1 and 3 years, respectively. The pregnancy rate was significantly higher in the secondary infertile group. The study of various sperm factors and the occurrence of pregnancy showed that they were not of equal significance in predicting male fertility potential. The percentage of pregnancies decreased significantly only when the sperm concentration was less than 5 x 10(6)/ml. The pregnancy rate increased significantly with the percentage of motile sperm. The percentage of sperm with normal morphology was also found to be significantly higher when a pregnancy occurred than when the couple remained infertile (43.6% vs 37.7%). In a detailed morphological analysis of the sperm, six abnormalities (microcephaly, double head, amorphous head, cytoplasmic droplet, bent tail and coiled tail) were found to be significantly more frequent when a pregnancy did not occur. The most predictive value was given by the Multiple Anomalies Index (MAI), which is the mean number of abnormalities observed per abnormal sperm. The pregnancy rate was significantly lower after both 1 and 3 years when the MAI was greater than 1.6. Multivariate analysis showed that the best prognostic indicator of fertility was given by the percentage of motile sperm and the MAI, particularly in patients with primary infertility.

Two groups of men were retrospectively selected according to their observed success in in-vitro fertilization. Seminal and post-migration sperm samples from a low fertilization rate group (less than or equal to 33% cleaved embryos) have been compared to results obtained from a high fertilization rate group (greater than or equal to 66%). It was found that a low mean value of the amplitude of lateral sperm head displacement and an increased percentage of abnormal acrosomes were related to in-vitro fertilization failure. None of the individual sperm factors studied was found to determine in-vitro fertilization success with certainty; only when they were considered in combination was it possible to predict the likelihood of successful in-vitro fertilization of human oocytes.

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Male microchimerism is frequent in the adult female liver and is attributed to fetal cells originating from previous male offspring. It has never been studied in pregnant women, female children, or fetuses. We examined its frequency and cellular nature in normal and diseased female livers from fetal life to adulthood. Forty-six liver samples from 29 women, 6 female children, and 11 female fetuses were screened for the Y chromosome via polymerase chain reaction (PCR) assay and fluorescent in situ hybridization (FISH). The X chromosome was used as an internal control. A third PCR assay was used for Y genotyping. The Y chromosome was detected in 5 of 6 children, 7 of 11 fetuses, 3 of 9 women with normal liver, 7 of 10 women with chronic hepatitis C, 5 of 6 women with acute liver disease during pregnancy with male offspring, and 2 of 4 nonpregnant women with fulminant hepatitis. In positive samples, the mean XY/XX ratio was 0.012 (؎0.004). In women, male microchimerism was correlated with previous male offspring. Male

As activation of telomerase represents a key step in the malignant transformation process, experimental models to develop anti-telomerase drugs provide a rational basis for anticancer strategies. We analysed the short and longterm efficacy of a stably expressed dominant-negative mutant (DN) of the telomerase catalytic unit (hTERT) in UT-7 and U937 human leukemia cell lines by using an IRES-e-GFP retrovirus. As expected, telomerase inactivation resulted in drastic telomere shortening, cytogenetic instability and cell growth inhibition in all e-GFP positive DN clones after 15 -35 days of culture. However, despite this initial response, 50% of e-GFP positive DN clones with short telomeres escaped from crisis after 35 days of culture and recovered a proliferation rate similar to the control cells. This rescue was associated with a telomerase reactivation inducing telomere lengthening. We identified two pathways, one involving the loss of the DN transgene expression and the other the transcriptional up-regulation of endogenous hTERT with persistence of the DN transgene expression. Although this second mechanism appears to be a very rare event (one clone), these findings suggest that genomic instability induced by short telomeres after telomerase inhibition might enhance the probability of activation or selection of telomere maintenance mechanisms dependent on hTERT transcription.

Microcinematographic analysis (50 framesisec) of the movement of 57 ejaculated human spermatozoa showed a heterogeneity of the flagellar parameters (velocity of the wave development (Vd), velocity of the wave propagation (Vc), beat frequency) corresponding to that of head trajectories (progressive velocity and amplitude of the lateral head displacement). According to our results the interdoublet sliding velocity might control the progressive velocity of the spermatozoa through the wave propagation velocity. The presence of the principal bend on the proximal part of the flagellum (20 pm) might inhibit the initiation of a new wave. The complex relation existing between Vc and Vd seems to indicate that the two velocities are partly independent of one another.

A prospective study of 394 infertile men was conducted over 3 years following a primary semen analysis. Simple comparisons between the groups of men whose partners conceived and those that did not, showed that the mean duration of infertility in the primary infertile group was significantly shorter when a pregnancy was observed, while age differed significantly between the two populations in the secondary infertile group. Multivariate analyses, taking these variables and sperm characteristics into account, showed that prognostic variables for the occurrence of pregnancy were the duration of infertility, sperm motility and the multiple anomalies index in the primary infertile group, and age of the male partner and percentage of normal sperm in the secondary infertile group. Tables for estimating the probability of observing a pregnancy as a function of these criteria are presented. In this study no positive influence of treatment on the occurrence of a pregnancy was found during the 3 years following the first semen analysis.